Introduction: Fibroblast growth-factor receptor (FGFR) inhibition is a promising strategy of treatment in urothelial cancer (UC). FGFR3 mutations or fusions (mut/fus) are common in luminal-1 UC subtype, which exhibits poor responses to immunotherapy. Erdafitinib is a potent and selective pan-FGFR tyrosine kinase inhibitor. Based on the results of the phase 2 BLC2001 trial (NCT02365597), in which erdafitinib showed an overall response rate of 40% in metastatic UC with FGFR3 mut/fus, it is the first approved targeted therapy in metastatic UC. Areas covered: This review covers the preclinical and clinical evidence for erdafitinib, summarizes the results of other FGFR inhibitors tested in UC and explores future perspectives of FGFR inhibition in UC. Expert opinion: In the era of precision medicine, erdafitinib approval marks a step forward in UC. Erdafitinib qualifies as a compelling comparator in the salvage therapy setting. Special attention must be paid to typical adverse class-effects of FGFR inhibitors. In the near future, in order to achieve an optimal selection of molecularly-altered tumors, it will be important to assess the performance of different diagnostic tools and to investigate the role of liquid biopsy. Combinations with immunotherapy represent a novel therapeutic opportunity being tested in ongoing trials.
Keywords: alterations; Erdafitinib; systemic therapy; targeted therapy; urothelial carcinoma.